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Nucleic Acids Research Advance Access originally published online on June 13, 2008
Nucleic Acids Research 2008 36(12):4149-4157; doi:10.1093/nar/gkn366
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Nucleic Acids Research, 2008, Vol. 36, No. 12 4149-4157
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Genomics

Cis-regulatory modules in the mammalian liver: composition depends on strength of Foxa2 consensus site

Geetu Tuteja1,2, Shane T. Jensen3, Peter White1 and Klaus H. Kaestner1,*

1Department of Genetics, 2Genomics and Computational Biology Graduate Group, University of Pennsylvania School of Medicine and 3Department of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA 19104, USA

*To whom correspondence should be addressed. Tel: +1 215 898 8759; Fax: +1 215 573 5892; Email: kaestner{at}mail.med.upenn.edu

Received March 20, 2008. Revised May 21, 2008. Accepted May 22, 2008.

Foxa2 is a critical transcription factor that controls liver development and plays an important role in hepatic gluconeogensis in adult mice. Here, we use genome-wide location analysis for Foxa2 to identify its targets in the adult liver. We then show by computational analyses that Foxa2 containing cis-regulatory modules are not constructed from a random assortment of binding sites for other transcription factors expressed in the liver, but rather that their composition depends on the strength of the Foxa2 consensus site present. Genes containing a cis-regulatory module with a medium or weak Foxa2 consensus site are much more liver-specific than the genes with a strong consensus site. We not only provide a better understanding of the mechanisms of Foxa2 regulation but also introduce a novel method for identification of different cis-regulatory modules involving a single factor.


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